The goal of this research is to develop thermal therapy modeling techniques and prototype applicators that combine ultrasound (US) and radio-frequency (RF) electro-magnetic (EM) phased arrays which are designed for treating locally advanced cancer in the intact breast. The proposed hybrid RF/US applicators will combine regional RE heating with local US heating to improve the temperature distributions relative to those which are presently achievable in the clinic with adjuvant hyperthermia using RF or US applicators alone. These hybrid RE/US phased array devices will facilitate the clinical application of emerging cancer therapies, including the delivery and release of thermosensitive liposome-encapsulated drugs. The strategy for achieving this goal will: 1. evaluate parametric simulation models of the thermal distributions produced by hybrid RF/US applicators; 2. optimize beamforming approaches for the hybrid RF/US phased array system; and 3. design, develop, and test prototype hybrid RF/US thermal therapy systems for locally advanced breast cancer. The modeling approach will calculate RF field contributions and combine these results with simulations of US fields. The combined heating contributions produced by hybrid RE/US phased arrays will be optimized such that temperature distribution in the target volume is improved and problems with normal tissue heating are reduced or eliminated. The modeling and optimization results will also specify candidate geometries for RF/US phased array systems that target locally advanced cancer in the intact breast. Based on these modeling and optimization results, a prototype hybrid RF/US phased array system will be constructed. Anticipated success with the computer modeling, prototype construction, and preliminary device evaluation will ultimately translate into human clinical trials.